Mass spectrometry (MS) is an indispensable analytical tool in modern chemical analysis, due to its detection sensitivity and specificity. Evolution of ionization methods results in a breakthrough for the application of MS analysis. The development of ionization techniques enables mass spectrometry to assist different field of analysis. Classical electron ionization and chemical ionization assist the analysis of volatile hydrocarbons and small organic pollutants. Nowadays, electrospray ionization and matrix-assisted laser desorption/ionization empower the development of biological MS for supporting various aspects of life science research (e.g. proteomics, metabolomics, and drug discovery). Recently, desorption/ionization techniques under atmospheric pressure for direct sample analysis by MS are becoming popular. The development of convenient and efficient atmospheric desorption/ionization techniques would expand the application of MS for the direct analysis of daily-life samples (e.g. food, pharmaceutical products) with simple and fast analytical procedure, and possibly bring MS from laboratory to the field.
The currently available atmospheric desorption/ionization techniques can be classified into electrospray-based, energetic particle-based, laser-based and coupled techniques. Desorption Electrospray Ionization (DESI) is an electrospray-based technique using a jet of solvent ions and molecules with nebulizing gas to hit the surface of sample for in-situ extraction of analyte molecules, and ionization and desorption of analyte ions. Low Temperature Plasma (LTP) Probe and Direct Analysis in Real Time (DART) techniques are energetic particle-based desorption/ionization techniques. LTP probe utilizes plasma of helium gas atoms/ions/radicals generated from dielectric barrier discharge. Molecules desorbed from sample surface by the thermal energy of the LTP would then be ionized via charge transfer reaction with the charged species in LTP. Similarly, DART generates excited/metastable helium atom via electrical discharge. Desorption of analyte molecules is resulted from a thermal process in addition to bombardment of excited atoms/ions. Femtosecond infrared laser is another type of an intense energy source employed for ambient desorption/ionization of analytes from solid sample for MS analysis. Analyte would be desorbed via thermal desorption, and ionization is believed to take place via the charge exchange reaction between charged species and neutral analyte molecules. Moreover, coupled techniques employ two desorption/ionization techniques to accomplish desorption and ionization separately. For instance, Laser Ablation Electrospray Ionization (LAESI) is a coupled technique employing laser desorption and subsequent electrospray ionization of neutral analyte. Recently, an atmospheric desorption/ionization techniques namely Field-induced Direct Ionization (using an electrical potential of 3-5 kV) has been reported for the direct detection of secondary metabolites of small living organisms (such as scorpion and toad). Nevertheless, all of these mentioned techniques require assisting reagents such as solvents and inert gases to operate, which can complicate matters. Types of samples that can be analyzed by currently available ambient ionization mass spectrometric methods are also limited to small-sized samples only.
The use of assisting reagents (e.g. helium) imposes additional reagent costs for operation, and also requires extra instrumentation (e.g. solvent supply system, vacuum pumping system) for the supply and removal of these reagents. Furthermore, the use of solvent causes the technique to become incompatible to solvent-sensitive samples. In addition, the change in identity/composition of these assisting reagents may lower the analytical performances of these atmospheric desorption/ionization techniques. For the Field-induced Direct Ionization technique, similar to other atmospheric ionization techniques, it is also confined to small organisms due to limitations in low ionization efficiency. In addition, it is limited to small and sharp samples as the relatively low electrical potential is used for the ionization of analyte molecules.
Hence, there is a need for atmospheric desorption/ionization method and system for MS, which is capable of directly generating ion from large-sized (and also small-sized) samples, without the use of assisting reagents (e.g. solvent, gas).